"Success for me is having a significant impact on dengue disease in communities," says Scott O'Neill, holding a container of mosquitoes.

Colyn Huber

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Originally published on July 6, 2012 1:26 pm

First of a two-part series

This summer, my big idea is to explore the big ideas of science. Instead of just reporting science as results — the stuff that's published in scientific journals and covered as news — I want to take you inside the world of science. I hope I'll make it easier to understand how science works, and just how cool the process of discovery and innovation really is.

A lot of science involves failure, but there are also the brilliant successes, successes that can lead to new inventions, new tools, new drugs — things that can change the world

That got me thinking that I wanted to dive deeper into the story of an Australian scientist named Scott O'Neill. Scott had come up a clever new way for combating dengue fever.

Dengue is a terrible disease. It sickens tens of millions and kills tens of thousands. There's no cure, no vaccine and pretty much no way to prevent it. It's one of those diseases transmitted by a mosquito, like malaria.

About 20 years ago, a lot of scientists got excited about the idea of genetically modifying mosquitoes so they couldn't transmit these diseases. People are still pursuing this approach. But I thought genetically modifying mosquitoes would be really hard to do. Even if you were able to make these disease-blocking mosquitoes in the lab, I didn't see how you would ever get them to survive in the wild, and displace the disease-transmitting mosquitoes that were already there. There was also a societal problem with the scheme. Most people probably wouldn't be thrilled about having swarms of genetically modified mosquitoes released in their backyards.

But last summer, when I read about O'Neill's work, it really knocked me out. His big idea was to infect mosquitoes with a naturally occurring bacteria called Wolbachia. Turns out that by some unknown quirk of biology, Wolbachia-infected mosquitoes can't carry the dengue virus.

Let me repeat that, because this is a key point: A mosquito infected with the bacteria called Wolbachia can't transmit the virus that causes dengue. One microbe defeats the other.

When I interviewed O'Neill by phone last year, he told me the idea seemed to be working. He had released his Wolbachia-infected mosquitoes into two small communities in northeastern Australia.

"Over a very short period of time, the Wolbachia was able to invade the wild mosquito population until close to 100 percent of all mosquitoes had the Wolbachia infection — and so we presume, greatly reduced ability to transmit dengue between people," O'Neill told me.

That was enough success for me to do a short news story about O'Neill's work. But I knew there was more. I convinced my editor to let me go to Australia to learn more about O'Neill and his big idea.

'Incredibly Frustrating Work'

One of the first things I learned when I got to his lab at Monash University in Melbourne was a surprise: It had taken O'Neill 20 years to get his big idea to work.

"You know, I was incredibly persistent in not wanting to give this idea up," O'Neill said. "I thought the idea was a good idea, and I don't think you get too many ideas in your life, actually. At least I don't. I'm not smart enough. So I thought this idea was a really good idea."

The problem was that O'Neill couldn't figure out how to infect mosquitoes with Wolbachia. Remember, a Wolbachia infected mosquito can't transmit dengue.

You can't just spread Wolbachia bacteria around and hope the mosquitoes catch it. Instead, you have to puncture a mosquito egg or embryo about the size of a poppy seed with a hair-thin needle containing the bacteria, peering through a microscope the entire time so you can see what you're doing.

"It's incredibly frustrating work," O'Neill says.

His colleague Tom Walker spends hour after hour, day after day, trying to inject the embryos. Even though he's become an expert at this, Walker can do no more than 500 a day.

Then the scientists have to wait a week until the adult mosquitoes emerge to see if any are infected with Wolbachia. Walker says in this latest round of work he's injected 18,000 eggs — with nothing to show for it. "The success rate is very low," says Walker, in something of an understatement.

"We don't have any windows that can open in this building, so people like Tom can't jump out of them," O'Neill adds with a laugh. He sounds like he's only half kidding.

The good news is that if you can manage to get the bacteria into even one mosquito, nature will take care of spreading it for you. Any mommy mosquito that's infected will also infect all her darling offspring, all 100 or more of them. And when those baby mosquitoes become mature in about 10 days, the new mommies among them will pass Wolbachia to their babies. Pretty soon, everybody who's anybody in that mosquito community is infected.

Success: 'A Significant Impact On Dengue Disease In Communities'

Now as I said, O'Neill has been pushing this idea of using Wolbachia to control dengue for decades, for a most of that time without any success. I asked him what it takes to stick with something for that long.

"I think being obsessive," he replied. "Being maybe a little ill in that regard. And it's just that I seem to have focused my obsession onto Wolbachia instead of on to postage stamps or model trains."

And even though his obsession has brought him to the point where he's shown he can get his Wolbachia-infected mosquitoes to spread in the wild, that's not the success he's ultimately after. "Success for me is having a significant impact on dengue disease in communities," he says.

To do that, he'll have to release his mosquitoes in a place where there's a lot of dengue, and then see if that brings down the number of cases of the disease in humans. Those studies are being planned now.

The stakes are high. By some estimates, more than a billion people around the world are at risk for getting dengue. Even if it doesn't kill you, I'm told a case of dengue can make you feel so bad, you wish you were dead.

"[It's] pretty much the worst disease I've ever had. It was not fun," says Steven Williams, a tropical disease researcher at Smith College in Northampton, Mass. Williams was bitten by a dengue mosquito while on a trip to French Polynesia. He says for 10 days he had a high fever, horrible headache and terrible pain in his muscles and joints.

One other delightful thing about dengue: There are no specific drugs to treat it. "You basically just have to ride it out," says Williams.

Moments Of Triumph, With Trepidation

With no cure and no vaccine, O'Neill's Wolbachia-infected mosquitoes could make a huge difference. Although proving that is still years off, there have been moments of triumph in the 20-year slog that's brought him this far.

Take the day in 2006, when one of O'Neill's graduate students told him he thought he'd finally succeeded in infecting a dengue mosquito with Wolbachia.

I figured this must have been a red-letter day for O'Neill, a day of sheer elation. He told me looking back on it, it was. But at the time it didn't seem that way.

"Because ... you're so used to failure, and you don't believe anything when you see it," he says. "And so you can think back to when there was a eureka moment, but at the time, it's probably ... 'This looks pretty good but, you know, I've been burnt thousands of times before. Let's go and do it again, and let's do it another time, and check and check and check, and make sure it's actually real.' "

O'Neill says the day his team really enjoyed was last year when they tested to see if their mosquitoes would take over from the other mosquitoes in the wild.

O'Neill's colleague Scott Ritchie recorded the event for posterity on his cellphone.

That got me interested in O'Neill's work last summer. He and his colleagues have now completed a second release, and the results are looking promising. But O'Neill says it's not yet time to celebrate.

"We've got some good preliminary data, and we're on the path. And it's looking good. But you know I am a realist. It could fall over at any day," he says.

Copyright 2012 National Public Radio. To see more, visit http://www.npr.org/.

This week, we're starting a new project, taking us behind the scenes in science, looking at how scientists and inventors create new things and answer big questions about our world. This idea on how innovation happens came from NPR science correspondent Joe Palca, so we've come up with what we think is an appropriate name for the project. We're calling it Joe's Big Idea.

JOE PALCA, BYLINE: Great name. Wish I'd thought of it. The plan really is to talk about scientists' big ideas. So today, I'm going to talk to you about an Australian scientist who has a big idea about how to put a dent in a devastating global disease.

But before I tell you about the idea, I've got to tell you about the disease. It's called dengue fever. Even if you've heard of it, you might not know how bad it is. In fact, I wasn't entirely clear myself, so I called someone who knew first hand.

STEVEN WILLIAMS: Pretty much the worst disease I've ever had. It was not fun.

PALCA: That's Steven Williams. He's a college professor in Massachusetts. He's a friend of a high school buddy of mine. Dengue is transmitted by a mosquito. Williams was bitten while on a trip to French Polynesia.

PALCA: Williams also had terrible pain in his muscles and joints. Dengue is sometimes called break-bone fever.

WILLIAMS: But I'd say the worst thing for me was the headache. The head pain was pretty awful.

PALCA: Oh, and one other delightful thing about dengue: There are no specific drugs to treat it.

WILLIAMS: You basically just have to ride it out.

PALCA: Ten miserable days, and then a few weeks of feeling like a wrung-out dishrag. That's if you're lucky. Tens of thousands of people die each year from a severe form of the disease known as dengue hemorrhagic fever.

Dengue isn't a big problem in the United States, but with climate change, it could become one. There are scientists working on all sorts of ways to combat dengue, but I'm going to tell you about what Scott O'Neill is working on. His idea is to focus on the mosquito that transmits the disease. He's found a way to infect mosquitoes with a bacteria called Wolbachia. It's a naturally occurring bacteria that's harmless to humans.

Why does he do this? Well, it turns out that Wolbachia-infected mosquitoes can't carry the dengue virus. Let me repeat that: Scott O'Neill infects mosquitoes with the bacteria called Wolbachia because a Wolbachia-infected mosquito can't carry the dengue virus. No one knows exactly why, but it seems that somehow one microbe defeats the other.

Last year, he released his Wolbachia mosquitoes into two small communities in northeastern Australia.

SCOTT O'NEILL: Over a very short period of time, the Wolbachia was able to invade the wild mosquito population until close to 100 percent of all mosquitoes had the Wolbachia infection, and so we presume, greatly reduced ability to transmit dengue between people.

PALCA: That's from a phone interview I did with O'Neill last summer. I thought O'Neill was really on to something, so I did a radio story about his work. Normally, that would've been the end of it. But with this new beat, I have a chance to tell you more of the story, more about O'Neill and how he got his big idea to work. So I told my editor I needed to go visit O'Neill in Australia.

ANNE GUDENKAUF: What?

PALCA: It took a little convincing, but I can be persuasive. And after all, there's nothing like Australia.

PALCA: You probably know this already, but Australia is a long ways off.

(SOUNDBITE OF AIRPLANE ENGINES)

O'NEILL: You ready?

(SOUNDBITE OF DOOR OPENING)

PALCA: When I finally got to O'Neill's lab in Melbourne, I learned something surprising. It took O'Neill 20 years to get his big idea to work.

O'NEILL: You know, I was incredibly persistent about not wanting to give this idea up. I thought the idea was a good idea and, you know, and I don't think you get too many good ideas in your life, actually. At least I don't. I'm not smart enough. But - so I thought this idea was a really good idea.

PALCA: There was just one problem with this good idea. It didn't work - at least not at first. The problem was he couldn't get the Wolbachia bacteria to infect mosquitoes. It's really hard to do that in a laboratory. You have to puncture a mosquito egg or embryo about the size of a poppy seed with a hair-thin needle containing the bacteria, peering through a microscope the entire time so you can see what you're doing.

O'NEILL: Oh, it's incredibly frustrating work.

PALCA: O'Neill's colleague Tom Walker is the microinjection expert in O'Neill's lab. He says Tom spends hour a day at it.

O'NEILL: He can make it to 500 in a day.

PALCA: Then you have to wait a week until the eggs become larvae and then pupae and then adult mosquitoes to see if any are infected with Wolbachia. Tom says in this latest round of work, he's injected 18,000 eggs with nothing to show for it.

TOM WALKER: The success rate's very low, very low.

O'NEILL: And we don't have any windows that can open in this building, so that people like Tom can't jump out of them.

(LAUGHTER)

PALCA: O'Neill was only partly kidding about that, I can tell you. Anyway, the good news is that if you can manage to get the bacteria into even one mosquito, nature will take care of spreading it for you - because any mommy mosquito that's infected will also infect all her darling offspring, all 100 or more of them. And when those baby mosquitoes become mature in about 10 days, the new mommies among them will pass Wolbachia to their babies. Pretty soon, everybody who's anybody in that mosquito community is infected.

Turns out I'm infected females don't breed very effectively when Wolbachia is around. So pretty soon everybody who's anybody in that mosquito community is infected with Wolbachia.

Now as I said, Scott's been pushing this idea of using Wolbachia to control dengue for decades - for a most of that time without any success. I asked him what it takes to stick with something for that long.

O'NEILL: Well, I think I'm being obsessive. Being maybe a little, maybe, ill in that regard. And it's just that I seem to have focused my obsession onto Wolbachia rather than on to postage stamps or model trains.

PALCA: And even though his obsession has brought him to the point where he's shown he can get his Wolbachia-infected mosquitoes to spread in the wild, that's not the success he's ultimately after.

O'NEILL: Success for me is having a significant impact on dengue disease in communities.

PALCA: Although, that ultimate goal is still years, if not decades off, there have been moments of triumph in the 20 year slog that's brought them this far.

I figured this must have been a red-letter day for O'Neill, a day of sheer elation. O'Neil told me, looking back on it, it was. But at the time, it didn't seem that way.

O'NEILL: Because, you know, you're so used to failure and you don't believe anything when you see it. And so you can think back to when there was a eureka moments, but at the time, it's you're like oh, this looks pretty good but, you know, I've been burnt thousands of times before. Let's go and do it again, and let's do it another time, and check and check and make sure it's actually real.

PALCA: That's science in a nutshell. You want to be really sure about your result before you believe in yourself, let alone tell the world about it.

There was one day when O'Neill and his team were able to enjoy in real-time. It was the day last year when they tested to see if their mosquitoes would take over from the other mosquitoes in the wild. A small crowd had gathered to watch.

SCOTT RITCHIE: The inaugural release of the Wolbachia mosquitoes.

PALCA: O'Neill's colleague Scott Ritchie recorded the event for posterity on his cell phone. It doesn't look like a big deal. In the shaky video, you can see Scott O'Neill wearing jeans and a khaki shirt, walking past a red picket fence and up the driveway of a modest suburban house in a community in northeast Australia. He's carrying a small plastic container, like the ones you get potato salad in.

O'NEILL: One, two, three.

PALCA: He pries off the lid, and gives the container a shake.

O'NEILL: There they go. Smile for the camera, Scott.

PALCA: That was in 2011. A year later, O'Neill says all the mosquitoes in the two communities where they released their mosquitoes are now infected with Wolbachia.

He and his colleagues have now released their mosquitoes in two more communities and the results are looking promising. But O'Neill says it's not time to celebrate.

O'NEILL: We've got some good preliminary data, and we're on the path. And it's looking good. But, you know, I am a realist. It could fall over at any day.

PALCA: Somehow, even if that happens, I don't think O'Neill's going to give up.

Tomorrow, I'll tell you more about the challenges a scientist faces when his work starts to be successful.

Joe Palca, NPR News.

(SOUNDBITE OF MUSIC)

GREENE: And you can see video of that first release of mosquitoes that Joe mentioned, and also read more about Scott O'Neill's big ideas at our website NPR.org.